The Prostate最新文献

{"title":"Spatial and temporal patterns of prostate cancer burden and their association with Socio-Demographic Index in Asia, 1990-2019.","authors":"Li-Sha Luo,&nbsp;Jun-Feng Jiang,&nbsp;Hang-Hang Luan,&nbsp;Hao Zi,&nbsp;Cong Zhu,&nbsp;Bing-Hui Li,&nbsp;Xian-Tao Zeng","doi":"10.1002/pros.24258","DOIUrl":"https://doi.org/10.1002/pros.24258","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is the second most frequently diagnosed cancer for males worldwide, but the spatial and temporal trends of prostate cancer burden remain unknown in Asia. This study aimed to investigate the changing spatial and temporal trends of incidence, prevalence, mortality, disability-adjusted life year (DALY), and mortality-to-incidence ratio (MIR) of prostate cancer, and their association with the Socio-Demographic Index (SDI) in 48 Asian countries from 1990 to 2019.</p><p><strong>Methods: </strong>Data were extracted from the Global Health Data Exchange query tool, covering 48 Asian countries from 1990 to 2019. The average annual percent change was calculated to evaluate temporal trends. Spatial autocorrelation analysis was used to obtain spatial patterns, and the association between SDI and prostate cancer burden was estimated using a spatial panel model.</p><p><strong>Results: </strong>In Asia, the age-standardized incidence and prevalence of prostate cancer increased in almost all countries, and its mortality and DALY also increased in over half of the countries. Significantly regional disparities were found in Asia, and the hot spots for incidence, prevalence, mortality, and DALY were all located in Western Asia, the hot spots of percent change also occurred in Western Asia for incidence and DALY. Furthermore, SDI had a positive association with mortality (coef = 2.51, 95% confidence interval [CI]: 2.13-2.90) and negative association with DALY (coef = -14.99, 95% CI: -20.37 to -9.60) and MIR (coef = -0.95, 95%CI: -0.99 to -0.92).</p><p><strong>Conclusions: </strong>Prostate cancer burden increased rapidly throughout Asia and substantial disparities had persisted between countries. Geographically targeted interventions are needed to reduce the prostate cancer burden throughout Asia and in specific countries.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"193-202"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39554240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall and progression-free survival of Afro-Caribbean men with metastatic castration-resistant prostate cancer (mCRPC).","authors":"Pierre-Gilles Vestris,&nbsp;Gilles Gourtaud,&nbsp;Cédric Senechal,&nbsp;Yvanne Sadreux,&nbsp;Virginie Roux,&nbsp;Pascal Blanchet,&nbsp;Laurent Brureau","doi":"10.1002/pros.24270","DOIUrl":"https://doi.org/10.1002/pros.24270","url":null,"abstract":"<p><strong>Introduction: </strong>Several studies in the Caucasian population have shown the benefit of using docetaxel, abiraterone, or enzalutamide for patients with metastatic prostate cancer at the castration-resistant stage (mCRPC). However, there are no strong data for men of African ancestry. The objective of this study was to estimate the overall and progression-free survival of patients according to these treatments at the mCRPC stage.</p><p><strong>Patients and methods: </strong>This was a monocentric retrospective study that consecutively included 211 men with mCRPC between June 1, 2009 and August 31, 2020. The primary end point was overall survival (OS). The secondary end point was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed.</p><p><strong>Results: </strong>The present study included 180 patients for analyses. There was no difference in OS (log-rank test = 0.73), with a median follow-up of 20.7 months, regardless of the treatment administered in the first line. Men with mCRPC who received hormonotherapy (abiraterone or enzalutamide) showed better progression-free survival than those who received docetaxel (log-rank test = 0.004), with a particular interest for abiraterone hazard ratio (HR) = 0.51 (95% confidence interval: 0.39-0.67). The patient characteristics were similar, except for bone lesions, irrespective of the treatment administered in the first line. After univariate then multivariate analysis, only World Health Organization status and metastases at diagnosis were significantly associated with progression.</p><p><strong>Conclusion: </strong>Our results suggest the use of hormonotherapy (abiraterone or enzalutamide) with a tendency for abiraterone in first line for men with African ancestry at the mCRPC stage.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"269-275"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of adverse pathology features in grade group 2 prostatectomy specimens with syn- or metachronous metastatic disease.","authors":"Christopher Ma,&nbsp;Michelle Downes,&nbsp;Rahi Jain,&nbsp;Marc Ientilucci,&nbsp;Neil Fleshner,&nbsp;Nathan Perlis,&nbsp;Theodorus van der Kwast","doi":"10.1002/pros.24279","DOIUrl":"https://doi.org/10.1002/pros.24279","url":null,"abstract":"To validate the importance of recently established adverse histopathology features (cribriform pattern and intraductal carcinoma) as contra‐indication for deferred treatment of Gleason score 7 (3 + 4) (grade group [GG] 2) prostate cancer, we investigated their frequency in GG2 radical prostatectomies with syn‐ or metachronous metastatic disease.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"345-351"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39703557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Don't throw the baby out with the bath water.","authors":"Patrick J Horsley,&nbsp;Andrew Kneebone,&nbsp;Thomas N Eade,&nbsp;George Hruby","doi":"10.1002/pros.24284","DOIUrl":"https://doi.org/10.1002/pros.24284","url":null,"abstract":"Dear Editor, We read with interest the recently published article “Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.” The authors conducted a SEER database review and concluded that external beam radiotherapy (EBRT) does not affect survival in an elderly population of patients with metastatic prostate cancer. We agree that it is likely that not all elderly patients with metastatic disease benefit from local radiotherapy to the prostate. However, we are concerned that a significant subcohort that derives substantial benefit from local radiotherapy is lost in this large database study that is severely limited by a lack of granularity and randomization. Our strongest criticism is that the authors do not specify the site, intent nor dose and fractionation schedule of the EBRT delivered to the patients in this study, which renders the results uninterpretable. The survival benefit demonstrated in the STAMPEDE trial was from high‐dose radiotherapy to the prostate. It is quite plausible that many (or even the majority) of the patients in the study by Wenzel et al. received palliative radiotherapy for painful bone metastases, which would not be expected to benefit survival and could conceivably correlate with more advanced or aggressive disease. Furthermore, the patients in this study were not stratified by the burden of metastatic disease. In the STAMPEDE trial, it was only patients with a low burden of metastatic disease (defined as visceral metastases or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis) for whom a survival benefit to high‐dose radiotherapy to the prostate was demonstrated. In the unselected population of the STAMPEDE trial, there was no survival benefit to prostate radiotherapy. Similarly, subgroup analysis of the HORRAD trial also found a trend to benefit in those with lower metastatic burden, statistical significance perhaps obscured by a higher cut‐off of &lt;5 metastases. Redemonstration of the same result in the population unselected by the burden of disease by Wenzel et al. should not be taken as a refutation of the survival benefit seen in the low metastatic burden subgroup of the STAMPEDE trial. Even for patients with a low burden of metastatic disease treated with high‐dose radiotherapy to the prostate, survival is not the only end‐point of interest. Durable local control may prevent subsequent local complications. The NCIC CTC PR.3/MRC UK PR07 trial randomized patients with high risk or locally advanced prostate cancer to androgen deprivation therapy with or without local radiotherapy. One hundred eleven of 602 patients in the androgen deprivation therapy (ADT) alone group (compared to only 14 of 603 patients in the ADT plus radiotherapy group) progressed locally, with just over half of those with local progression receiving radiotherapy for presumably symptomatic disease. Radiotherapy when delivered at the time of castrate resistance is less likely ","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"397-398"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39725339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to the letter to the editor: \"Don't throw the baby out with the bath water\" by Horsley et al.","authors":"Mike Wenzel,&nbsp;Claudia Collà Ruvolo,&nbsp;Christoph Würnschimmel,&nbsp;Luigi Nocera,&nbsp;Pierre I Karakiewicz","doi":"10.1002/pros.24282","DOIUrl":"https://doi.org/10.1002/pros.24282","url":null,"abstract":"Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy Martini‐Klinik Prostate Cancer Center, University Hospital Hamburg‐Eppendorf, Hamburg, Germany Division of Experimental Oncology, Department of Urology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"399-400"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39725344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metagenomics studies for the diagnosis and treatment of prostate cancer.","authors":"Ali Zarei,&nbsp;Hossein Javid,&nbsp;Sara Sanjarian,&nbsp;Sara Senemar,&nbsp;Hanieh Zarei","doi":"10.1002/pros.24276","DOIUrl":"https://doi.org/10.1002/pros.24276","url":null,"abstract":"<p><strong>Aim: </strong>Mutation occurs in the prostate cell genes, leading to abnormal prostate proliferation and ultimately cancer. Prostate cancer (PC) is one of the most common cancers amongst men, and its prevalence worldwide increases relative to men's age. About 16% of the world's cancers are the result of microbes in the human body. Impaired population balance of symbiosis microbes in the human reproductive system is linked to PC development.</p><p><strong>Discussion: </strong>With the advent of metagenomics science, the genome sequence of the microbiota of the human body has been unveiled. Therefore, it is now possible to identify a higher range of microbiome changes in PC tissue via the Next Generation Technique, which will have positive consequences in personalized medicine. In this review, we intend to question the role of metagenomics studies in the diagnosis and treatment of PC.</p><p><strong>Conclusion: </strong>The microbial imbalance in the men's genital tract might have an effect on prostate health. Based on next-generation sequencing-generated data, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodetes are the nine frequent phyla detected in a PC sample, which might be involved in inducing mutation in the prostate cells that cause cancer.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"289-297"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39773804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate weight and prostate cancer outcomes after radical prostatectomy: Results from the SEARCH cohort study.","authors":"Sean Kennedy Barlow,&nbsp;Taofik Oyekunle,&nbsp;Jessica L Janes,&nbsp;Amanda M De Hoedt,&nbsp;William J Aronson,&nbsp;Christopher J Kane,&nbsp;Christopher L Amling,&nbsp;Matthew R Cooperberg,&nbsp;Zachary W Klaassen,&nbsp;Martha K Terris,&nbsp;Stephen J Freedland,&nbsp;Ilona Csizmadi","doi":"10.1002/pros.24283","DOIUrl":"https://doi.org/10.1002/pros.24283","url":null,"abstract":"<p><strong>Background: </strong>Smaller prostates have been linked to unfavorable clinical characteristics and poor short-term outcomes following radical prostatectomy (RP). We examined the relation between prostate weight at RP and prostate cancer (PC) outcomes post-RP.</p><p><strong>Methods: </strong>Men in the SEARCH cohort undergoing RP between 1988 and 2017 (N = 6242) were studied for PC-specific mortality (PCSM) as the primary outcome, and for biochemical recurrence (BCR), castration-resistant PC (CRPC) and metastasis as secondary outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were determined for associations between prostate weight and outcomes using Fine-Gray competing risk regression multivariable analyses. Sensitivity analyses were also carried out following exclusion of: (i) men with extreme prostate weights (<20 g and ≥100 g); and (ii) men with elevated prostate specific antigen (PSA) levels.</p><p><strong>Results: </strong>Median values for age, pre-RP PSA and prostate weight were 63 years, 6.6 ng/ml, and 42.0 g, respectively. During a median follow-up of 7.9 years, 153 (3%) died from PC, 2103 (34%) had BCR, 203 (3%) developed CRPC, and 289 (5%) developed metastases. Prostate weight was not associated with PCSM in the main analyses (multivariable HR = 1.43; 95% CI: 0.87-2.34) or in sensitivity analyses. Prostate weight was inversely associated with BCR in the main analyses (multivariable HR = 0.70; 95%CI: 0.61-0.79) which was unchanged in sensitivity analyses. HRs for prostate weight and CRPC and metastasis were elevated but statistical significance was not attained. Similar results were observed in sensitivity analyses.</p><p><strong>Conclusions: </strong>Inconsistent results for prostate weight and short-term vs longer-term outcomes highlight the need to better understand the complex biology leading to prostate size and the relevance of prostate size as a predictor of PC outcomes.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"366-372"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39725342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic syndrome and prostate cancer in Afro-Caribbean men.","authors":"Florian Lefebvre,&nbsp;Anne Blanchet-Deverly,&nbsp;Leah Michineau,&nbsp;Pascal Blanchet,&nbsp;Luc Multigner,&nbsp;Laurent Brureau","doi":"10.1002/pros.24281","DOIUrl":"https://doi.org/10.1002/pros.24281","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Metabolic syndrome (MetS) is a group of risk factors that increases the likelihood of developing cardiovascular diseases. Although suggested, the relationship between MetS and prostate cancer (PCa) is still inconclusive. Very few studies have addressed this question in populations of African descent, which are disproportionately affected by PCa. This study aimed to assess the prevalence of MetS among incident cases of Afro-Caribbean PCa and estimate its association with adverse clinicopathological features and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP).</p><p><strong>Materials and methods: </strong>We included 285 consecutive patients with incident cases of PCa attending the University Hospital of Guadeloupe (French West Indies). MetS was evaluated at the time of diagnosis by collecting information on blood pressure, glycaemic status, triglyceride and high-density lipoprotein cholesterol levels, and obesity through various surrogates, including two waist circumference indicators (≤94 cm, ≥102 cm), the waist-to-hip ratio (≥0.95), and body mass index (BMI; ≥30 kg/m² ). We followed 245 patients who underwent RP as primary treatment of localized PCa.</p><p><strong>Results: </strong>The prevalence of MetS varied greatly, from 31.6% to 16.4%, when a waist circumference ≥94 cm or BMI were used as obesity surrogates, respectively. No significant associations were found between MetS, regardless of the obesity criteria employed, and the risk of adverse pathological features or BCR.</p><p><strong>Conclusions: </strong>The high variability in MetS resulting from the diversity of obesity criteria used may explain the discordant associations reported in the literature. Further studies using strict and uniform criteria to define MetS on homogeneous ethnic groups are encouraged to clarify the association, if any, between MetS and PCa outcomes.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"359-365"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39723937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the 2012 and 2018 US preventive services task force prostate cancer screening guidelines on pathologic outcomes after prostatectomy.","authors":"Benjamin D Plambeck,&nbsp;Luke L Wang,&nbsp;Samantha Mcgirr,&nbsp;Jinfeng Jiang,&nbsp;Bryant J Van Leeuwen,&nbsp;Chad A Lagrange,&nbsp;Shawna L Boyle","doi":"10.1002/pros.24261","DOIUrl":"https://doi.org/10.1002/pros.24261","url":null,"abstract":"<p><strong>Background: </strong>In May 2018, the US Preventive Services Task Force (USPSTF) recommended prostate cancer (PCa) screening for ages 55-69 be an individual decision. This changed from the USPSTF's May 2012 recommendation against screening for all ages. The effects of the 2012 and 2018 updates on pathologic outcomes after prostatectomy are unclear.</p><p><strong>Methods: </strong>This study included 647 patients with PCa who underwent prostatectomy at our institution from 2005 to 2018. Patient groups were those diagnosed before the 2012 update (n = 179), between 2012 and 2018 updates (n = 417), and after the 2018 update (n = 51). We analyzed changes in the age of diagnosis, pathologic Gleason grade group (pGS), pathologic stage, lymphovascular invasion (LVI), and favorable/unfavorable pathology. Multivariable logistic regression adjusting for pre-biopsy covariables (age, prostate-specific antigen [PSA], African American race, family history) assessed impacts of 2012 and 2018 updates on pGS and pathologic stage. A p  < 0.05 was statistically significant.</p><p><strong>Results: </strong>Median age increased from 60 to 63 (p = 0.001) between 2012 and 2018 updates and to 64 after the 2018 update. A significant decrease in pGS1, pGS2, pT2, and favorable pathology (p < 0.001), and a significant increase in pGS3, pGS4, pGS5, pT3a, and unfavorable pathology (p < 0.001) was detected between 2012 and 2018 updates. There was no significant change in pT3b or LVI between 2012 and 2018 updates. On multivariable regression, diagnosis between 2012 and 2018 updates was significantly associated with pGS4 or pGS5 and pT3a (p < 0.001). Diagnosis after the 2018 update was significantly associated with pT3a (p = 0.005). Odds of pGS4 or pGS5 were 3.2× higher (p < 0.001) if diagnosed between 2012 and 2018 updates, and 2.3× higher (p = 0.051) if after the 2018 update. Odds of pT3a were 2.4× higher (p < 0.001) if diagnosed between 2012 and 2018 updates and 2.9× higher (p = 0.005) if after the 2018 update.</p><p><strong>Conclusions: </strong>The 2012 USPSTF guidelines negatively impacted pathologic outcomes after prostatectomy. Patients diagnosed between 2012 and 2018 updates had increased frequency of higher-risk PCa and lower frequency of favorable disease. In addition, data after the 2018 update demonstrate a continued negative impact on postprostatectomy pathology. Thus, further investigation of the long-term effects of the 2018 USPSTF update is warranted.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"216-220"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39646368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination therapy with novel androgen receptor antagonists and statin for castration-resistant prostate cancer.","authors":"Hiroshi Nakayama,&nbsp;Yoshitaka Sekine,&nbsp;Daisuke Oka,&nbsp;Yoshiyuki Miyazawa,&nbsp;Seiji Arai,&nbsp;Hidekazu Koike,&nbsp;Hiroshi Matsui,&nbsp;Yasuhiro Shibata,&nbsp;Kazuhiro Suzuki","doi":"10.1002/pros.24274","DOIUrl":"https://doi.org/10.1002/pros.24274","url":null,"abstract":"<p><strong>Background: </strong>One of the growth mechanisms of castration-resistant prostate cancer (CRPC) is de novo androgen synthesis from intracellular cholesterol, and statins may be able to inhibit this mechanism. In addition, statins have been reported to suppress the expression of androgen receptors (ARs) in prostate cancer cell lines. In this study, we investigated a combination therapy of novel AR antagonists and statin, simvastatin, for CRPC.</p><p><strong>Methods: </strong>LNCaP, 22Rv1, and PC-3 human prostate cancer cell lines were used. We developed androgen-independent LNCaP cells (LNCaP-LA). Microarray analysis was performed, followed by pathway analysis, and mRNA and protein expression was evaluated by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. Cell viability was determined by MTS assay and cell counts. All evaluations were performed on cells treated with simvastatin and with or without AR antagonists (enzalutamide, apalutamide, and darolutamide).</p><p><strong>Results: </strong>The combination of darolutamide and simvastatin most significantly suppressed proliferation in LNCaP-LA and 22Rv1 cells. In a 22Rv1-derived mouse xenograft model, the combination of darolutamide and simvastatin enhanced the inhibition of cell proliferation. In LNCaP-LA cells, the combination of darolutamide and simvastatin led to reduction in the mRNA expression of the androgen-stimulated genes, KLK2 and PSA; however, this reduction in expression did not occur in 22Rv1 cells. The microarray data and pathway analyses showed that the number of differentially expressed genes in the darolutamide and simvastatin-treated 22Rv1 cells was the highest in the pathway termed \"role of cell cycle.\" Consequently, we focused our efforts on the cell cycle regulator polo-like kinase 1 (PLK1), cyclin-dependent kinase 2 (CDK2), and cell cycle division 25C (CDC25C). In 22Rv1 cells, the combination of darolutamide and simvastatin suppressed the mRNA and protein expression of these three genes. In addition, in PC-3 cells (which lack AR expression), the combination of simvastatin and darolutamide enhanced the suppression of cell proliferation and expression of these genes.</p><p><strong>Conclusions: </strong>Simvastatin alters the expression of many genes involved in the cell cycle in CRPC cells. Thus, the combination of novel AR antagonists (darolutamide) and simvastatin can potentially affect CRPC growth through both androgen-dependent and androgen-independent mechanisms.</p>","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":" ","pages":"314-322"},"PeriodicalIF":2.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39788768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}